Digestive System and How It Works

The digestive system.

T
he digestive system is made up of the digestive tract—a series
of hollow organs joined in a long, twisting tube from the mouth to
the anus—and other organs that help the body break down and
absorb food (see figure).Organs that make up the digestive tract
are the mouth, esophagus, stomach, small intestine, large
intestine
—also called the colon—rectum, and anus. Inside these hollow
organs is a lining called
the mucosa. In the mouth, stomach, and small intestine, the
mucosa contains tiny glands that produce juices to help digest
food. The digestive tract also contains a layer of smooth muscle that helps
break down food and move it along the tract.
Two “solid” digestive organs, the liver and the pancreas, produce
digestive juices that reach the intestine through small tubes called
ducts. The gallbladder stores the liver’s digestive juices until they
are needed in the intestine. Parts of the nervous and circulatory
systems also play major roles in the digestive system.
Why is digestion important?
When you eat foods—such as bread, meat, and vegetables—
they are not in a form that the body can use as nourishment.
Food and drink must be changed into smaller molecules of
nutrients before they can be absorbed into the blood and carried to cells
throughout the body. Digestion is the process by which food and drink are
broken down into their smallest parts so the body can use them to build and
nourish cells and to provide energy.
How is food digested?
Digestion involves mixing food with digestive juices, moving it through the
digestive tract, and breaking down large molecules of food into smaller
molecules. Digestion begins in the mouth, when you chew and swallow, and
is completed in the small intestine.
Movement of Food Through the System
The large, hollow organs of the digestive tract contain a layer of muscle that
enables their walls to move. The movement of organ walls can propel food
and liquid through the system and also can mix the contents within each
organ. Food moves from one organ to the next through muscle action called
peristalsis. Peristalsis looks like an ocean wave traveling through the muscle.
The muscle of the organ contracts to create a narrowing and then propels
the narrowed portion slowly down the length of the organ. These waves of
narrowing push the food and fluid in front of them through each hollow
organ.
The first major muscle movement occurs when food or liquid is swallowed.
Although you are able to start swallowing by choice, once the swallow
begins, it becomes involuntary and proceeds under the control of the nerves.
Swallowed food is pushed into the esophagus, which connects the throat
above with the stomach below. At the junction of the esophagus and
stomach, there is a ringlike muscle, called the lower esophageal sphincter,
closing the passage between the two organs. As food approaches the closed
sphincter, the sphincter relaxes and allows the food to pass through to the
stomach.
The stomach has three mechanical tasks. First, it stores the swallowed food
and liquid. To do this, the muscle of the upper part of the stomach relaxes to
accept large volumes of swallowed material. The second job is to mix up the
food, liquid, and digestive juice produced by the stomach. The lower part of
the stomach mixes these materials by its muscle action. The third task of the
stomach is to empty its contents slowly into the small intestine.
Several factors affect emptying of the stomach, including the kind of food
and the degree of muscle action of the emptying stomach and the small
intestine. Carbohydrates, for example, spend the least amount of time in the
stomach, while protein stays in the stomach longer, and fats the longest. As
the food dissolves into the juices from the pancreas, liver, and intestine, the
contents of the intestine are mixed and pushed forward to allow further
digestion.
Finally, the digested nutrients are absorbed through the intestinal walls and
transported throughout the body. The waste products of this process include
undigested parts of the food, known as fiber, and older cells that have been
shed from the mucosa. These materials are pushed into the colon, where
they remain until the feces are expelled by a bowel movement.
Production of Digestive Juices
The digestive glands that act first are in the mouth—the salivary glands.
Saliva produced by these glands contains an enzyme that begins to digest
the starch from food into smaller molecules. An enzyme is a substance that
speeds up chemical reactions in the body.
The next set of digestive glands is in the stomach lining. They produce
stomach acid and an enzyme that digests protein. A thick mucus layer coats
the mucosa and helps keep the acidic digestive juice from dissolving the
tissue of the stomach itself. In most people, the stomach mucosa is able to
resist the juice, although food and other tissues of the body cannot.
After the stomach empties the food and juice mixture into the small
intestine, the juices of two other digestive organs mix with the food. One of
these organs, the pancreas, produces a juice that contains a wide array of
enzymes to break down the carbohydrate, fat, and protein in food. Other
enzymes that are active in the process come from glands in the wall of the
intestine.
The second organ, the liver, produces yet another digestive juice—bile. Bile
is stored between meals in the gallbladder. At mealtime, it is squeezed out of
the gallbladder, through the bile ducts, and into the intestine to mix with the
fat in food. The bile acids dissolve fat into the watery contents of the
intestine, much like detergents that dissolve grease from a frying pan. After
fat is dissolved, it is digested by enzymes from the pancreas and the lining of
the intestine.
Absorption and Transport of Nutrients
Most digested molecules of food, as well as water and minerals, are
absorbed through the small intestine. The mucosa of the small intestine
contains many folds that are covered with tiny fingerlike projections called
villi. In turn, the villi are covered with microscopic projections called
microvilli. These structures create a vast surface area through which
nutrients can be absorbed. Specialized cells allow absorbed materials to
cross the mucosa into the blood, where they are carried off in the
bloodstream to other parts of the body for storage or further chemical
change. This part of the process varies with different types of nutrients.
Carbohydrates. The Dietary Guidelines for Americans 2005 recommend
that 45 to 65 percent of total daily calories be from carbohydrates. Foods
rich in carbohydrates include bread, potatoes, dried peas and beans, rice,
pasta, fruits, and vegetables. Many of these foods contain both starch and
fiber.
The digestible carbohydrates—starch and sugar—are broken into simpler
molecules by enzymes in the saliva, in juice produced by the pancreas, and
in the lining of the small intestine. Starch is digested in two steps. First, an
enzyme in the saliva and pancreatic juice breaks the starch into molecules
called maltose. Then an enzyme in the lining of the small intestine splits the
maltose into glucose molecules that can be absorbed into the blood. Glucose
is carried through the bloodstream to the liver, where it is stored or used to
provide energy for the work of the body.
Sugars are digested in one step. An enzyme in the lining of the small
intestine digests sucrose, also known as table sugar, into glucose and
fructose, which are absorbed through the intestine into the blood. Milk
contains another type of sugar, lactose, which is changed into absorbable
molecules by another enzyme in the intestinal lining.
Fiber is undigestible and moves through the digestive tract without being
broken down by enzymes. Many foods contain both soluble and insoluble
fiber. Soluble fiber dissolves easily in water and takes on a soft, gel-like
texture in the intestines. Insoluble fiber, on the other hand, passes
essentially unchanged through the intestines.
Protein. Foods such as meat, eggs, and beans consist of giant molecules of
protein that must be digested by enzymes before they can be used to build
and repair body tissues. An enzyme in the juice of the stomach starts the
digestion of swallowed protein. Then in the small intestine, several enzymes
from the pancreatic juice and the lining of the intestine complete the
breakdown of huge protein molecules into small molecules called amino
acids. These small molecules can be absorbed through the small intestine
into the blood and then be carried to all parts of the body to build the walls
and other parts of cells.
Fats. Fat molecules are a rich source of energy for the body. The first step in
digestion of a fat such as butter is to dissolve it into the watery content of
the intestine. The bile acids produced by the liver dissolve fat into tiny
droplets and allow pancreatic and intestinal enzymes to break the large fat
molecules into smaller ones. Some of these small molecules are fatty acids
and cholesterol. The bile acids combine with the fatty acids and cholesterol
and help these molecules move into the cells of the mucosa. In these cells
the small molecules are formed back into large ones, most of which pass into
vessels called lymphatics near the intestine. These small vessels carry the
reformed fat to the veins of the chest, and the blood carries the fat to
storage depots in different parts of the body.
Vitamins. Another vital part of food that is absorbed through the small
intestine are vitamins. The two types of vitamins are classified by the fluid in
which they can be dissolved: water-soluble vitamins (all the B vitamins and
vitamin C) and fat-soluble vitamins (vitamins A, D, E, and K). Fat-soluble
vitamins are stored in the liver and fatty tissue of the body, whereas water-
soluble vitamins are not easily stored and excess amounts are flushed out in
the urine.
Water and salt. Most of the material absorbed through the small intestine
is water in which salt is dissolved. The salt and water come from the food
and liquid you swallow and the juices secreted by the many digestive glands.
[Top]
How is the digestive process controlled?
Hormone Regulators
The major hormones that control the functions of the digestive system are
produced and released by cells in the mucosa of the stomach and small
intestine. These hormones are released into the blood of the digestive tract,
travel back to the heart and through the arteries, and return to the digestive
system where they stimulate digestive juices and cause organ movement.
The main hormones that control digestion are gastrin, secretin, and
cholecystokinin (CCK):
Gastrin causes the stomach to produce an acid for dissolving and digesting
some foods. Gastrin is also necessary for normal cell growth in the lining of
the stomach, small intestine, and colon.
Secretin causes the pancreas to send out a digestive juice that is rich in
bicarbonate. The bicarbonate helps neutralize the acidic stomach contents
as they enter the small intestine. Secretin also stimulates the stomach to
produce pepsin, an enzyme that digests protein, and stimulates the liver to
produce bile.
CCK causes the pancreas to produce the enzymes of pancreatic juice, and
causes the gallbladder to empty. It also promotes normal cell growth of the
pancreas.
Additional hormones in the digestive system regulate appetite:
Ghrelin is produced in the stomach and upper intestine in the absence of
food in the digestive system and stimulates appetite.
Peptide YY is produced in the digestive tract in response to a meal in the
system and inhibits appetite.
Both of these hormones work on the brain to help regulate the intake of food
for energy. Researchers are studying other hormones that may play a part in
inhibiting appetite, including glucagon-like peptide-1 (GPL-1), oxyntomodulin
(+ ), and pancreatic polypeptide.
Nerve Regulators
Two types of nerves help control the action of the digestive system.
Extrinsic, or outside, nerves come to the digestive organs from the brain or
the spinal cord. They release two chemicals, acetylcholine and adrenaline.
Acetylcholine causes the muscle layer of the digestive organs to squeeze
with more force and increase the “push” of food and juice through the
digestive tract. It also causes the stomach and pancreas to produce more
digestive juice. Adrenaline has the opposite effect. It relaxes the muscle of
the stomach and intestine and decreases the flow of blood to these organs,
slowing or stopping digestion.
The intrinsic, or inside, nerves make up a very dense network embedded in
the walls of the esophagus, stomach, small intestine, and colon. The intrinsic
nerves are triggered to act when the walls of the hollow organs are stretched
by food. They release many different substances that speed up or delay the
movement of food and the production of juices by the digestive organs.
Together, nerves, hormones, the blood, and the organs of the digestive
system conduct the complex tasks of digesting and absorbing nutrients from
the foods and liquids you consume each day.

Zollinger-Ellison syndrome: A rare disorder caused by a tumor called a gastrinoma, most often occurring in the
pancreas. The tumor secretes the hormone gastrin, which causes increased production of gastric acid leading to
severe recurrent ulcers of the esophagus, stomach, and the upper portions of the small intestine (the duodenum and
jejunum).

Gastrinomas resulting in the Zollinger-Ellison syndrome are not limited to the pancreas but may also occur in the
stomach, duodenum, spleen and lymph nodes.

The treatment of the Zollinger-Ellison syndrome includes the use of H2 antagonists (for example cimetidine [brand
name: Tagamet] and ranitidine [Zantac]) and the proton pump inhibitors (for example, lansoprazole [Prevacid] and
omeprazole [Prilosec]). The H2 antagonists block the action of histamine on stomach cells, thus reducing stomach
acid production. The proton pump inhibitors also block the production of acid by the stomach cells. Surgical removal
of the tumor is curative in about 25% of cases.

The syndrome is named for two American surgeons Robert M. Zollinger (1903-1992) and Edwin H. Ellison (1918-
1970).

What is a proton pump?

The proton pump is a molecule in certain cells of the stomach. It "pumps" acid into the stomach. It
takes a non-acidic potassium ion out of the stomach and replaces it with an acidic hydrogen ion. This
hydrogen ion is what makes things acidic. By putting more hydrogen ions into your stomach, the
pump makes the contents of your stomach more acidic. But by stopping the action of the pump, acid
secretion into the stomach is stopped.

Are there differences among PPIs?

PPIs are similar in how they work, and there is no evidence that one is more effective than another.
However, they differ in how they are broken down by the liver and how they interact with other
medications. Also, the effects of some PPIs may last longer than others, and may be taken less
frequently.

How are PPIs different from H2 Blockers?

Both PPIs and H2 Blockers suppress gastric acid secretion. They are different, however, in how they
do this. While PPIs shut down the proton pumps in the stomach, H2 Blockers work by blocking the
histamine receptors in acid producing cells in the stomach.

PPIs have a delayed onset of action, while H2 blockers ranitidine .foemetidine etc begin working
within an hour. PPIs work for a longer period of time; most up to 24 hours and the effects may last up
to three days. H2 Blockers, however, usually only work up to 12 hours.

——————

What are the different types of PPIs?

PPIs include:
• Aciphex (raberprazole)
• Kapidex (dexlansoprazole)
• Nexium (esomeprazole)
• Prevacid (lansoprazole)
• Prilosec (omeprazole)
• Protonix (pantoprazole)

The Parietal Cell: Mechanism of Acid Secretion

Parietal cells contain an extensive secretory network (called canaliculi) from which the
HCl is secreted by active transport into the stomach. The enzyme hydrogen potassium
ATPase (H+/K+ ATPase) is unique to the parietal cells and transports the H+ against a
concentration gradient of about 3 million to 1, which is the steepest ion gradient formed
in the human body.
The best-known component of gastric juice is hydrochloric acid, the secretory product of
the parietal, or oxyntic cell. It is known that the capacity of the stomach to secrete HCl is
almost linearly related to parietal cell numbers. When stimulated, parietal cells secrete
HCl at a concentration of roughly 160 mM (equivalent to a pH of 0.8). The acid is
secreted into large cannaliculi, deep invaginations of the plasma membrane which are
continuous with the lumen of the stomach. When acid secretion is stimulated there is a
dramatic change in the morphology of the membranes of the parietal cell. Cytoplasmic
tubulovesicular membranes which are abundant in the resting cell virtually disappear in
concert with a large increase in the cannalicular membrane. It appears that the proton
pump as well as potassium and chloride conductance channels initially reside on
intracellular membranes and are transported to and fused into the cannalicular membrane
just prior to acid secretion. The epithelium of the stomach is intrinsically resistant to the
damaging effects of gastric acid and other insults. Nonetheless, excessive secretion of
gastric acid is a major problem in human and, to a lesser extent, animal populations,
leading to gastritis, gastric ulcers and peptic acid disease. As a consequence, the parietal
cell and the mechanisms it uses to secrete acid have been studied extensively, leading to
development of several drugs useful for suppressing acid secretion.
Mechanism of Acid Secretion
The hydrogen ion concentration in parietal cell secretions is roughly 3 million fold
higher than in blood, and chloride is secreted against both a concentration and electric
gradient. Thus, the ability of the partietal cell to secrete acid is dependent on active
transport.
The key player in acid secretion is a H+/K+ ATPase or "proton pump" located in the
cannalicular membrane. This ATPase is magnesium-dependent, and not inhibitable by
ouabain. The current model for explaining acid secretion is as follows:
• Hydrogen ions are generated within the parietal cell from dissociation of water. The
hydroxyl ions formed in this process rapidly combine with carbon dioxide to form
bicarbonate ion, a reaction cataylzed by carbonic anhydrase.
• Bicarbonate is transported out of the basolateral membrane in exchange for
chloride. The outflow of bicarbonate into blood results in a slight elevation of blood
pH known as the "alkaline tide". This process serves to maintain intracellular pH in
the parietal cell.
• Chloride and potassium ions are transported into the lumen of the cannaliculus by
conductance channels, and such is necessary for secretion of acid.
• Hydrogen ion is pumped out of the cell, into the lumen, in exchange for potassium
through the action of the proton pump; potassium is thus effectively recycled.
• Accumulation of osmotically-active hydrogen ion in the cannaliculus generates an
osmotic gradient across the membrane that results in outward diffusion of water -
the resulting gastric juice is 155 mM HCl and 15 mM KCl with a small amount of
 NaCl.
These processes are depicted in the animation below.
Control of Acid Secretion
Parietal cells bear receptors for three stimulators of acid secretion, reflecting a
triumverate of neural, paracrine and endocrine control:
• Acetylcholine (muscarinic type receptor)
• Gastrin
• Histamine (H2 type receptor)
Histamine from enterochromaffin-like cells may well be the primary modulator, but the
magnitude of the stimulus appears to result from a complex additive or multiplicative
interaction of signals of each type. For example, the low amounts of histamine released
constantly from mast cells in the gastric mucosa only weakly stimulate acid secretion,
and similarly for low levels of gastrin or acetylcholine. However, when low levels of
each are present, acid secretion is strongly forced. Additionally, pharmacologic
antagonists of each of these molecules can block acid secretion.
Histamine's effect on the parietal cell is to activate adenylate cyclase, leading to
elevation of intracellular cyclic AMP concentrations and activation of protein kinase A
(PKA). One effect of PKA activation is phosphorylation of cytoskeletal proteins
involved in transport of the H+/K+ ATPase from cytoplasm to plasma membrane.
Binding of acetylcholine and gastrin both result in elevation of intracellular calcium
concentrations. The animation below depicts acid secretion by the parietal cell. Even
though many of the actors are unlabeled, you should be able to deduce the identity of all
the components you see. Several additional mediators have been shown to result in
gastric acid secretion when infused into animals and people, including calcium,
enkephalin and bombesin. Calcium and bombesin both simulate gastrin release, while
opiate receptors have been identified on parietal cells. It is unclear whether these
molecules have a significant physiologic role in parietal cell function.
A variety of substances are capable of reducing gastric acid secretion when infused
intravenously, including prostaglandin E2 and several peptides hormones, including
secretin, gastric inhibitory peptide, glucagon and somatostatin. PGE2, secretin and
somatostatin may be physiologic regulators. Somatostatin inhibits secretion of gastrin
and histamine, and appears to have a direct inhibitory effect on the parietal cell.

Acid production
Parietal cells produce gastric acid (hydrochloric acid) in response to histamine (via H2
receptors), acetylcholine (M3 receptors) and gastrin (CCK2 receptors). The histamine
receptors act by increasing intracellular cAMP, whereas the muscarinic and gastrin
receptors increase intracellular Ca2+ levels. Both cAMP and Ca2+ act via protein kinases
to increase the transport of acid into the stomach. Gastrin is more important indirectly by
increasing histamine synthesis in ECL cells[1], as gastrin has no effect on the maximum
histamin-stimulated gastric acid secretion [2].
Parietal cells contain an extensive secretory network (called canaliculi) from which the
HCl is secreted by active transport into the stomach. The enzyme hydrogen potassium
ATPase (H+/K+ ATPase) is unique to the parietal cells and transports the H+ against a
concentration gradient of about 3 million to 1, which is the steepest ion gradient formed
in the human body.
Hydrochloric acid is formed in the following manner:
• Hydrogen ions are formed from the dissociation of water molecules.
The enzyme carbonic anhydrase converts one molecule of carbon
dioxide and two molecules of water indirectly into a bicarbonate ion
(HCO3-) and a hydrogen ion (H+).
• The bicarbonate ion (HCO3-) is exchanged for a chloride ion (Cl-) on the
basal side of the cell and the bicarbonate diffuses into the venous
blood leading to an alkaline tide.
• Potassium (K+) and chloride (Cl-) ions diffuse into the canaliculi.
• Hydrogen ions are pumped out of the cell into the canaliculi in
exchange for potassium ions, via the H+/K+ ATPase.
The resulting highly-acidic environment causes proteins from food to unfold (or
denature), exposing the peptide bonds that link together amino acids. HCl also activates
pepsinogen, an endopeptidase, allowing it to help digestion by breaking specific peptide
bonds, a process known as proteolysis. Furthermore, the sudden increase in gastric acid
secretion following a meal can cause a physiological phenomenon called an alkaline
tide, which is due to the production and export of bicarbonate from parietal cells. The
alkaline tide is neutralized by the action of the pancreatic duct which produces a
bicarbonate secretion that is deposited into the lumen of the duct while the byproduct,
hydrogen ions, are pumped out the basal membrane into the portal blood stream, thereby
neutralizing the bicarbonate from the stomach.
Parietal cells secrete acid in response to three types of stimuli:
• H2 histamine receptors (most significant contribution)
• parasympathetic activity via the Vagus nerve and enteric nervous
system
• gastrin (least significant contribution, but note that histamine
secretion by ECL cells is due in part to gastrin)
Upon stimulation, adenylate cyclase is activated within the parietal cells. This increases
intracellular cyclic AMP, which leads to activation of protein kinase A. Protein kinase A
phosphorylates proteins involved in the transport of H+/K+ ATPase from the cytoplasm
to the cell membrane. This causes resorption of K+ ions and secretion of H+ ions. The pH
of the secreted fluid can fall 'by' 0.8.

Intrinsic factor
Parietal cells also produce intrinsic factor. Intrinsic factor is required for the absorption
of vitamin B12 in the diet. Atrophic Gastritis, in particular in the elderly, will cause an
inability to absorb B12 and can lead to deficiencies such as decreased DNA synthesis and
nucleotide metabolism in the bone marrow.

Canaliculus
A canaliculus is an adaptation found on gastric parietal cells. It is a deep infolding, or
little channel, which serves to increase the surface area, e.g. for secretion. The
membrane of parietal cells is dynamic; the numbers of canaliculi rise and fall according
to secretory need. This is accomplished by the fusion of canalicular precursors, or
"tubulovesicles", with the membrane to increase surface area, and the reciprocal
endocytosis of the canaliculi (reforming the tubulovesicles) to decrease it.

Diseases of parietal cells

• Peptic ulcers can result from over-acidity in the stomach. Antacids can
be used to enhance the natural tolerance of the gastric lining.
Antimuscarinic drugs such as pirenzepine or H2 antihistamines can
reduce acid secretion. Proton pump inhibitors are more potent at
reducing gastric acid production since that is the final common
pathway of all stimulation of acid production.
• In pernicious anemia, autoantibodies directed against parietal cells or
intrinsic factor cause a reduction in vitamin B12 absorption. It can be
treated with injections of replacement vitamin B12 (hydroxocobalamin
or cyanocobalamin).
• Achlorhydria is another autoimmune disease of the parietal cells. The
damaged parietal cells are unable to produce the required amount of
gastric acid. This leads to an increase in gastric pH, impaired digestion
of food and increased risk of gastroenteritis.
Physiology of Vomiting

At least after death you're not nauseous. (Woody Allen in Sleeper)

Vomiting is the forceful expulsion of contents of the stomach and often, the proximal
small intestine. It is a manifestation of a large number of conditions, many of which are
not primary disorders of the gastrointestinal tract. Regardless of cause, vomiting can
have serious consequences, including acid-base derangments, volume and electrolyte
depletion, malnutrition and aspiration pneumonia.
The Act of Vomiting
Vomiting is usually experienced as the finale in a series of three events, which everyone
reading this has experienced:
• Nausea is an unpleasant and difficult to describe psychic experience in humans and
probably animals. Physiologically, nausea is typically associated with decreased
gastric motility and increased tone in the small intestine. Additionally, there is often
reverse peristalsis in the proximal small intestine.
• Retching ("dry heaves") refers to spasmodic respiratory movements conducted with
a closed glottis. While this is occurring, the antrum of the stomach contracts and the
fundus and cardia relax. Studies with cats have shown that during retching there is
repeated herniation of the abdominal esophagus and cardia into the thoracic cavity
due to the negative pressure engendered by inspiratory efforts with a closed glottis.
 • Emesis or vomition is when gastric and often small intestinal contents are
propelled up to and out of the mouth. It results from a highly coordinated series of
events that could be described as the following series of steps (don't practice these
in public):
○ A deep breath is taken, the glottis is closed and the larynx is raised to open
the upper esophageal sphincter. Also, the soft palate is elevated to close off
the posterior nares.
○ The diaphragm is contracted sharply downward to create negative pressure
in the thorax, which facilitates opening of the esophagus and distal
esophageal sphincter.
○ Simultaneously with downward movement of the diaphragm, the muscles of
the abdominal walls are vigorously contracted, squeezing the stomach and
thus elevating intragastric pressure. With the pylorus closed and the
esophagus relatively open, the route of exit is clear.
The series of events described seems to be typical for humans and many animals, but is
not inevitable. Vomition occasionally occurs abruptly and in the absense of premonitory
signs - this situation is often referred to as projectile vomiting. A common cause of
projectile vomiting is gastric outlet obstruction, often a result of the ingestion of foreign
bodies.
An activity related to but clearly distinct from vomiting is regurgitation, which is the
passive expulsion of ingested material out of the mouth - this often occurs even before
the ingesta has reached the stomach and is usually a result of esophageal disease.
Regurgitation also is a normal component of digestion in ruminants.
There is also considerable variability among species in the propensity for vomition. Rats
reportedly do not vomit. Cattle and horses vomit rarely - this is usually an ominous sign
and most frequently a result of acute gastric distension. Carnivores such as dogs and cats
vomit frequently, often in response to such trivial stimuli as finding themselves on a
clean carpet. Humans fall between these extremes, and interestingly, rare individuals
have been identified that seem to be incapable of vomiting due to congenital
abnormalities in the vomition centers of the brainstem.
Control of Vomition
The complex, almost sterotypical set of
activities that culminate in vomiting
suggest that control is central, which
indeed has been shown to be true. Within
the brainstem are two anatomically and
functionally distinct units that control
vomiting:
Bilateral vomition centers in the
reticular formation of the medulla
integrate signals from a large number of
outlying sources and their excitement is
ultimately what triggers vomition.
Electric stimulation of these centers induces vomiting, while destruction of the vomition
centers renders animals very resistant to emetic drugs. The vomition centers receive
afferent signals from at least four major sources:
• The chemoreceptor trigger zone (see below)
• Visceral afferents from the gastrointestinal tract (vagus or sympathetic nerves) -
these signals inform the brain of such conditions as gastrointestinal distention (a
very potent stimulus for vomition) and mucosal irritation.
• Visceral afferents from outside the gastrointestinal tract - this includes signals
from bile ducts, peritoneum, heart and a variety of other organs. These inputs to the
vomition center help explain how, for example, a stone in the common bile duct can
result in vomiting.
• Afferents from extramedullary centers in the brain - it is clear that certain
psychic stimuli (odors, fear), vestibular disturbances (motion sickness) and cerebral
trauma can result in vomition.
The chemoreceptor trigger zone is a bilateral set of centers in the brainstem lying
under the floor of the fourth ventricle. Electrical stimulation of these centers does not
induce vomiting, but application of emetic drugs does - if and only if the vomition
centers are intact. The chemoreceptor trigger zones function as emetic chemoreceptors
for the vomition centers - chemical abnormalities in the body (e.g. emetic drugs, uremia,
hypoxia and diabetic ketoacidosis) are sensed by these centers, which then send
excitatory signs to the vomition centers. Many of the antiemetic drugs act at the level of
the chemoreceptor trigger zone.
To summarize, two basic sets of pathways - one neural and one humoral - lead to
activation of centers in the brain that initiate and control vomition. Think of the
vomition centers as commander in chief of vomition, who makes the ultimate decision.
This decision is based on input from a battery of advisors, among whom the
chemoreceptor trigger zone has considerable influence. This straighforward picture is
almost certainly oversimplified and flawed in some details, but helps to explain much of
the physiology and pharmacology of vomition.
Causes and Consequences of Vomiting
The myriad causes of vomiting are left as an exercise - come up with a list based on
personal experience and your understanding of the control of vomition. An important
point, however, is that many cases of vomiting are due to diseases outside of the
gastrointestinal tract.
Simple vomiting rarely causes problems, but on occasion, can lead to such serious
consequences as aspiration pneumonia. Additionally, severe or repetitive vomition
results in disturbances in acid-base balance, dehydration and electrolyte depletion. In
such cases, the goal is to rapidly establish a definitive diagnosis of the underlying
disease so that specific therapy can be instituted. This is often not easy and in many
cases, it is advantageous to administer antiemetic drugs in order to suppress vomition
and reduce its sequelae.